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Identification of epistasis through a partial advanced intercross reveals three arthritis loci within the Cia5 QTL in mice.

Johannesson, Martina LU ; Karlsson, Jenny C LU ; Wernhoff, P; Nandakumar, K S; Lindqvist, Anna-Karin LU ; Olsson, Lina LU ; Cook, A D; Andersson, Åsa LU and Holmdahl, Rikard LU (2005) In Genes and Immunity 6(3). p.175-185
Abstract
Identification of genes controlling complex diseases has proven to be difficult; however, animal models may pave the way to determine how low penetrant genes interact to promote disease development. We have dissected the Cia5/Eae3 susceptibility locus on mouse chromosome 3 previously identified to control disease in experimental models of multiple sclerosis and rheumatoid arthritis. Congenic strains showed significant but small effects on severity of both diseases. To improve the penetrance, we have now used a new strategy that defines the genetic interactions. The QTL interacted with another locus on chromosome 15 and a partial advanced intercross breeding of the two congenic strains for eight generations accumulated enough statistical... (More)
Identification of genes controlling complex diseases has proven to be difficult; however, animal models may pave the way to determine how low penetrant genes interact to promote disease development. We have dissected the Cia5/Eae3 susceptibility locus on mouse chromosome 3 previously identified to control disease in experimental models of multiple sclerosis and rheumatoid arthritis. Congenic strains showed significant but small effects on severity of both diseases. To improve the penetrance, we have now used a new strategy that defines the genetic interactions. The QTL interacted with another locus on chromosome 15 and a partial advanced intercross breeding of the two congenic strains for eight generations accumulated enough statistical power to identify interactions with several loci on chromosome 15. Thereby, three separate loci within the original QTL could be identified; Cia5 affected the onset of arthritis by an additive interaction with Cia31 on chromosome 15, whereas the Cia21 and Cia22 affected severity during the chronic phase of the disease through an epistatic interaction with Cia32 on chromosome 15. The definition of genetic interactions was a prerequisite to dissect the Cia5 QTL and we suggest the partial advanced intercross strategy to be helpful also for dissecting other QTL controlling complex phenotypes. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
partial advanced intercross, collagen-induced arthritis, quantitative trait locus
in
Genes and Immunity
volume
6
issue
3
pages
175 - 185
publisher
Nature Publishing Group
external identifiers
  • pmid:15716976
  • wos:000228691900001
  • scopus:18444416834
ISSN
1476-5470
DOI
10.1038/sj.gene.6364155
language
English
LU publication?
yes
id
b4da7599-8ac3-45de-b614-297397382f61 (old id 133697)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15716976&dopt=Abstract
date added to LUP
2007-07-16 09:00:11
date last changed
2017-01-01 04:49:41
@article{b4da7599-8ac3-45de-b614-297397382f61,
  abstract     = {Identification of genes controlling complex diseases has proven to be difficult; however, animal models may pave the way to determine how low penetrant genes interact to promote disease development. We have dissected the Cia5/Eae3 susceptibility locus on mouse chromosome 3 previously identified to control disease in experimental models of multiple sclerosis and rheumatoid arthritis. Congenic strains showed significant but small effects on severity of both diseases. To improve the penetrance, we have now used a new strategy that defines the genetic interactions. The QTL interacted with another locus on chromosome 15 and a partial advanced intercross breeding of the two congenic strains for eight generations accumulated enough statistical power to identify interactions with several loci on chromosome 15. Thereby, three separate loci within the original QTL could be identified; Cia5 affected the onset of arthritis by an additive interaction with Cia31 on chromosome 15, whereas the Cia21 and Cia22 affected severity during the chronic phase of the disease through an epistatic interaction with Cia32 on chromosome 15. The definition of genetic interactions was a prerequisite to dissect the Cia5 QTL and we suggest the partial advanced intercross strategy to be helpful also for dissecting other QTL controlling complex phenotypes.},
  author       = {Johannesson, Martina and Karlsson, Jenny C and Wernhoff, P and Nandakumar, K S and Lindqvist, Anna-Karin and Olsson, Lina and Cook, A D and Andersson, Åsa and Holmdahl, Rikard},
  issn         = {1476-5470},
  keyword      = {partial advanced intercross,collagen-induced arthritis,quantitative trait locus},
  language     = {eng},
  number       = {3},
  pages        = {175--185},
  publisher    = {Nature Publishing Group},
  series       = {Genes and Immunity},
  title        = {Identification of epistasis through a partial advanced intercross reveals three arthritis loci within the Cia5 QTL in mice.},
  url          = {http://dx.doi.org/10.1038/sj.gene.6364155},
  volume       = {6},
  year         = {2005},
}